Cervical carcinogenesis is a continuous pathological process from precancerous lesions to cancer, i.e. from atypical hyperplasia of the cervix to carcinoma in situ and eventually to invasive carcinoma. Therefore, all cervical lesions that may develop into cervical invasive carcinoma are collectively referred to as cervical precancerous lesions.
Focus on the diagnosis and treatment of cervical precancerous lesions
At present, there is a progressive understanding of cervical precancerous lesions. Cervical cytology (TCT) is a simple, feasible and accurate screening method, and human papillomavirus (HPV) is closely related to the development of cervical precancerous lesions. Early identification, treatment, and follow-up of cervical precancerous lesions can lead to a significant reduction in the incidence of cervical invasive cancer.
Risk factors for the development of cervical precancerous lesions
Risk factors for the development of cervical precancer include race, low social class, multiple births, premature births, smoking, long-term oral contraceptive use, and dietary factors, among which the age of first intercourse and the number of sexual partners are most relevant. Early age at first intercourse and the number of sexual partners are most likely to develop precancerous cervical lesions.
Human papillomavirus
HPV infection occurs in the vulva, perineum, and lower genital tract of sexually active women and is classified as a low or no risk virus, including HPV 6, 11, 42, 43, and 44, which are usually associated with condyloma acuminata or low-grade squamous intraepithelial lesions and rarely cause invasive cancer. High oncogenic risk viruses include HPV 16, 18 and 31, which are usually associated with CIN II, III and invasive carcinoma. There are also moderate oncogenic risk viruses, including HPV 33, 35, 39, 51, 52 and 56. It is now possible to detect HPV load in the body, which facilitates screening for cervical precancerous lesions and post-treatment follow-up.
Classification and nomenclature of cervical precancerous lesions
Cervical precancerous lesions to cervical cancer is a continuous pathological process. cervical intraepithelial neoplasia (CIN) is used to describe this cervical lesion that can develop into invasive carcinoma. cin I corresponds to mild atypical hyperplasia, cin II to moderate atypical hyperplasia, and cin III to severe atypical hyperplasia and carcinoma in situ. the name squamous intraepithelial lesion (SIL) was used again in 1988, which is considered to better reflect the nature of the lesion than CIN better reflects the nature of the lesion. It includes the terms low grade squamous intraepithelial lesion (LSIL) and high grade squamous intraepithelial disease (HSIL). Low grade SIL includes HPV infection and CIN I, and high grade SIL includes CIN II and CIN III. Both terms CIN and SIL are currently used clinically to describe cervical precancerous lesions.
Pathological features of cervical precancerous lesions
The basic pathological feature of cervical atypical hyperplasia is that the epithelial cells are both heterotypic and maintain the ability to differentiate. Mild atypical hyperplasia (CINⅠ): cells are limited to the lower 1/3 of the epithelial layer, cell heterogeneity is mild, and nuclear fission phase is visible. Moderate atypical hyperplasia (CIN II): cells are limited to the lower 2/3 of the epithelial layer, with obvious heterogeneity and more nuclear divisions. Severe atypical hyperplasia (CIN III): cells extend to the upper 2/3 of the epithelial layer or more with significant heterogeneity. Carcinoma in situ means that the whole layer of squamous epithelium is full of atypical hyperplastic cells, i.e. cancer cells; the epithelial stratification structure is lost and the cell polarity is lost; but the basement membrane is intact (if it penetrates the basement membrane, it is infiltrating cancer).
Symptoms and regression of cervical precancerous lesions
Most cervical precancerous lesions have no obvious symptoms; some patients show increased leucorrhea, contact bleeding or irregular vaginal bleeding. The main physical sign is cervical erosion. According to our statistics, more than 50% of cases of atypical hyperplasia have cervical erosion. In situ carcinoma, 75% to 85% of cases have this symptom. Therefore, it is again emphasized that patients with cervical erosion should undergo cervical cytology for cervical precancer screening, and further diagnosis and treatment methods should be decided based on the test results.
Not all cervical precancerous lesions will evolve into cervical cancer; the natural course of untreated cervical precancerous lesions can be characterized by three outcomes, namely lesion regression, persistence or lesion progression. According to statistics, without treatment, more than 40% of cases will develop into invasive cancer. it takes 3-8 years for CIN I and CIN II to progress to CIN III, and 10-15 years for CIN III to develop into invasive cancer. the chance of lesion progression increases significantly in patients under 35 years of age.
Diagnosis of cervical precancerous lesions
Cervical cytology smear is only a screening tool and cannot be used as a basis for diagnosis. Therefore, further colposcopy and colposcopic biopsy should be performed if the cervical cytology test results are abnormal. Colposcopy should be routinely performed for LSIL and HSIL. This is the main method to diagnose cervical lesions and cervical cancer based on the clarity of the lesion margins, the color of the white acetate test, the type of vascular structure and the reaction to iodine staining. There is a tendency to misuse colposcopy in the country and one should be wary of over-diagnosis and over-treatment. Cervical canal scraping should be performed in cases with internal migration of the squamocolumnar junction, suspicious lesions involving the cervical canal, and suspected adenocarcinoma.
Cervical conization is the gold standard for confirming the diagnosis of CIN III and invasive carcinoma: for cases where the squamocolumnar junction cannot be observed under colposcopy and the border of the lesion cannot be seen; cervical canal scraping reports CIN II and CIN III; colposcopy suspects occult infiltration and biopsy is CIN III; cytologic and histologic findings are different; suspicious adenocarcinoma; biopsy diagnoses microinvasive carcinoma.
Treatment and follow-up of cervical precancerous lesions
The aim of treatment of cervical precancerous lesions is local lesion control and prevention of lesion progression to higher grade atypical hyperplasia or invasive carcinoma. The prerequisite for treatment is a clear diagnosis of the nature and extent of the lesion by colposcopy and biopsy, especially to confirm the absence of infiltrating cancer. The purpose of treatment should be clarified based on the CIN grade, with reference to the HPV test results, so that treatment can be standardized. The choice of treatment method should be based on the patient’s age, marital status, lesion degree, scope level, as well as symptoms, follow-up and technical conditions, and the patient’s wishes, etc., so as to individualize the treatment.
CIN Ⅰ and HPV positive should be treated, for CIN Ⅰ and CIN Ⅱ mainly apply physical therapy (microwave, laser, etc.), CIN Ⅲ use cervical electrodesiccation (LEEP), conization is characterized by convenience, less damage, less bleeding, fast recovery, mainly for CINI, CIN Ⅱ. In contrast, the treatment used for CIN III has a significantly higher recurrence rate compared to conization, and is not recommended for early leaching cervical cancer.
It is important to distinguish diagnostic and therapeutic LEEP, to master the indications, and to avoid overtreatment. It is not advocated for cervical treatment with histologically confirmed CIN, and the treatment of cervical cancer in situ with LEEP is not promoted. For CIS that have undergone LEEP treatment, close follow-up is needed to be vigilant for recurrence. The misuse of LEEP exists in all large and small cities in China, and community physicians have an obligation to educate the general public on the health of women regarding the standardized treatment of cervical lesions.
Conjunctomy can treat CIN III, cervical carcinoma in situ, and stage Ia cervical cancer.
Total hysterectomy is suitable for highly squamous intraepithelial lesions without invasive carcinoma; no fertility requirements; combined with other gynecological diseases requiring surgical treatment; cervical canal lesions that are not cleaned by conization; postmenopausal cervical atrophy that prevents conization; and poor follow-up conditions. The surgical procedure can be transabdominal, transvaginal or laparoscopic hysterectomy. If the lesion involves the upper vaginal segment, it should be removed together.
All cervical precancerous lesions should be followed up regularly with TCT and HPV load after treatment, and if abnormalities are found during the follow-up, diagnostic treatment should be performed according to the above principles.